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Utrecht, Netherlands

Merkely B.,Semmelweis University | Roka A.,Semmelweis University | Kutyifa V.,Semmelweis University | Boersma L.,Heart Lung Center Utrecht | And 7 more authors.
Europace | Year: 2010

Cardiac resynchronization therapy (CRT) is a highly efficient treatment modality for patients with severe congestive heart failure and intraventricular dyssynchrony. However, the high individual cost and technical complexity of the implantation may limit its widespread utilization. The European Heart Rhythm Association (EHRA) launched a project to assess treatment of arrhythmias in all European Society of Cardiology member countries in order to have a platform for a progressive harmonization of arrhythmia treatment. As a result, two EHRA White Books have been published in 2008 and 2009 based on governmental, insurance, and professional society data. Our aim was to analyse the local differences in the utilization of CRT, based on these surveys. A total of 41 countries provided enough data to analyse years 2006-2008. Significant differences were found in the overall number of implantations and the growth rate between 2006 and 2008. Other contributing factors include local reimbursement of CRT, the existence of national guidelines, and a high number of conventional implantable cardioverter-defibrillator implantations, while GDP or healthcare spending has less effect. Focusing on improving these factors may increase the availability of CRT in countries where it is currently underutilized. © The Author 2010.

Van Laake L.W.,University of California at San Francisco | Van Laake L.W.,Heart Lung Center Utrecht | Qian L.,University of California at San Francisco | Cheng P.,University of California at San Francisco | And 4 more authors.
Circulation Research | Year: 2010

Rationale: Induced pluripotent stem (iPS) cells can differentiate into multiple cell types, including cardiomyocytes and have tremendous potential for drug discovery and regenerative therapies. However, it is unknown how much variability exists between differentiated lineages from independent iPS cell lines and, specifically, how similar iPS cell-derived cardiomyocytes (iPS-CMs) are to embryonic stem (ES) cell-derived cardiomyocytes (ES-CMs). Objective: We investigated how much variability exists between differentiated lineages from independent iPS cell lines and how similar iPS-CMs are to ES-CMs. Methods and Results: We generated mouse iPS cells in which expression of NKX2-5, an early cardiac transcription factor, was marked by transgenic green fluorescent protein (GFP). Isolation of iPS-and ES-derived NKX2-5-GFP+cardiac progenitor pools, marked by identical reporters, revealed unexpectedly high similarity in genome-wide mRNA expression levels. Furthermore, the variability between cardiac progenitors derived from independent iPS lines was minimal. The NKX2-5-GFP +iPS cells formed cardiomyocytes by numerous induction protocols and could survive upon transplantation into the infarcted mouse heart without formation of teratomas. Conclusions: Despite the line-to-line variability of gene expression in the undifferentiated state of ES and iPS cells, the variance narrows significantly in lineage-specific iPS-derived cardiac progenitors, and these progenitor cells can be isolated and used for transplantation without generation of unwanted cell types. © 2010 American Heart Association, Inc.

Lubinski A.,Medical University of Lodz | Bissinger A.,Medical University of Lodz | Boersma L.,Heart Lung Center Utrecht | Leenhardt A.,Lariboisiere University Hospital | And 6 more authors.
Europace | Year: 2011

Aims: Sudden cardiac death (SCD) is a major health concern in developed countries. Many studies have demonstrated the efficacy of implantable cardioverter defibrillator (ICD) therapy in the prevention of SCD and total mortality reduction. However, the high individual costs and the reimbursement policy may limit widespread ICD utilization. Methods and results: This study analyzed the temporal and the geographical trends of the ICD implantation rate. Data were gathered from two editions of the European Heart Rhythm Association (EHRA) White Books published in 2008 and 2009. The analysis revealed significant differences in the rates of ICD implantation per million capita between the countries, but the median implantations was constantly increasing. The number of ICD implantations correlated with gross domestic product (GDP), GDP per capita, expenditure on health, life expectancy, and the number of implanting centres. Conclusion: There are great number of differences in the ICD-implanting rates between EHRA member countries, consequent to the increase in the number of ICD implantations. The ICD implantation rates are related to national economic status and healthcare expenses. All rights reserved. © The Author 2011.

Sato H.,Imperial College London | Woodhead F.A.,Imperial College London | Ahmad T.,Peninsula Medical School | Grutters J.C.,Heart Lung Center Utrecht | And 10 more authors.
Human Molecular Genetics | Year: 2010

The HLA class II (DRB1 and DQB1) associations with sarcoidosis have been studied by several groups but often without consistent results. In this paper, we consider the hypothesis that observed inconsistencies relate to distinct, genetically encoded disease phenotypes which differ in prevalence between centres. We therefore typed HLA-DRB1 and DQB1 in 340 UK, 139 Dutch and 163 Japanese sarcoidosis patients and, respectively, 354, 218 and 168 healthy controls from these populations. We applied consistent phenotyping and genotyping and investigated associations between HLA class II alleles and distinct disease phenotypes within and between ethnic groups. DRB1*01 and DQB1*0501 are protective against all manifestations of sarcoidosis. Lung-predominant sarcoidosis is associated with DRB1*12 and *14. Löfgren's syndrome is a common sarcoidosis phenotype in the Dutch and is strongly associated with the DRB1*0301 allele. This phenotype is not seen among the Japanese in whom DRB1*0301 is absent. The same allele is protective for UK uveitis. Sarcoid uveitis is common in Japan. The DRB1*04-DQB1*0301 haplotype is a risk factor for this disease manifestation in Japanese and UK subjects but protective for sarcoidosis overall. We show that distinct sarcoidosis phenotypes have similar genetic associations across ethnic groups. The disease case mix differs between centres and may be explained by different ethnic allelic frequencies. © The Author 2010. Published by Oxford University Press. All rights reserved.

Van Laake L.W.,Heart Lung Center Utrecht | Van Donselaar E.G.,University Utrecht | Monshouwer-Kloots J.,Leiden University | Schreurs C.,Leiden University | And 6 more authors.
Cellular and Molecular Life Sciences | Year: 2010

Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins; (2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells.

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